ArticleGlia2019
Microglia damage precedes major myelin breakdown in X-linked adrenoleukodystrophy and metachromatic leukodystrophy.
Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 92 citations in OpenAlex.
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- Microglial clonal dynamics and the impact of clonal hematopoiesis in autologously transplanted rhesus macaques.Cell reports · 2026Article
- The complex lipidome as a driver of tissue-specific pathology in adrenoleukodystrophy.Molecular neurodegeneration · 2026Review
- Natural History of Clinical Phenotypes and Their Biochemical Correlates in Adult X-Linked Adrenoleukodystrophy.Journal of inherited metabolic disease · 2026Article
- Inflammation and Immunomodulation in Cerebral X-linked Adrenoleukodystrophy: Review of Pathology and Interventions.Journal of child neurology · 2026Review
- Peroxisomal integrity in demyelination-associated microglia enables cellular debris clearance and myelin renewal in mice.The Journal of clinical investigation · 2026Article
- Peroxisomes and the nervous system: progress and challenges in neuroinflammation and cell-specific functions.Frontiers in molecular neuroscience · 2026Article
- Multimodal quantitative MRI finds early brain changes in asymptomatic X-linked adrenoleukodystrophy.Brain communications · 2026Article
- An AAV-Based Therapy Approach for Neurological Phenotypes of X-Linked Adrenoleukodystrophy.International journal of molecular sciences · 2025Review
- Review
- Impaired peroxisomal beta-oxidation in microglia triggers oxidative stress and impacts neurons and oligodendrocytes.Frontiers in molecular neuroscience · 2025Article
- Inflammation's impact on the interaction between oligodendrocytes and axons.Discovery immunology · 2025Review
- Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The pathology of X-linked adrenoleukodystrophy: tissue specific changes as a clue to pathophysiology.Orphanet journal of rare diseases · 2024Review
- Role of Basal Forebrain Neurons in Adrenomyeloneuropathy in Mice and Humans.Annals of neurology · 2024Article
- Efficacy of HDAC Inhibitors in Driving Peroxisomal β-Oxidation and Immune Responses in Human Macrophages: Implications for Neuroinflammatory Disorders.Biomolecules · 2023Article
- SCA34 caused by ELOVL4 L168F mutation is a lysosomal lipid storage disease sharing pathology features with neuronal ceroid lipofuscinosis and peroxisomal disorders.Acta neuropathologica · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked adrenoleukodystrophy (X-ALD) and metachromatic leukodystrophy (MLD) are two relatively common examples of hereditary demyelinating diseases caused by a dysfunction of peroxisomal or lysosomal lipid degradation. In both conditions, accumulation of nondegraded lipids leads to the destruction of cerebral white matter. Because of their high lipid content, oligodendrocytes are considered key to the pathophysiology of these leukodystrophies. However, the response to allogeneic stem cell transplantation points to the relevance of cells related to the hematopoietic lineage. In the present study, we aimed to better characterize the pathogenetic role of microglia in the above-mentioned diseases. Applying recently established microglia markers to human autopsy cases of X-ALD and MLD we were able to delineate distinct lesion stages in evolving demyelinating lesions. The immune-phenotype of microglia was altered already early in lesion evolution, and microglia loss preceded full-blown myelin degeneration both in X-ALD and MLD. DNA fragmentation indicating phagocyte death was observed in areas showing microglia loss. The morphology and dynamics of phagocyte decay differed between the diseases and between lesion stages, hinting at distinct pathways of programmed cell death. In summary, the present study shows an early and severe damage to microglia in the pathogenesis of X-ALD and MLD. This hints at a central pathophysiologic role of these cells in the diseases and provides evidence for an ongoing transfer of toxic substrates primarily enriched in myelinating cells to microglia.
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